Journal Article

FZJ-2022-03681

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CLC Anion/Proton Exchangers Regulate Secretory Vesicle Filling and Granule Exocytosis in Chromaffin Cells

Comini, M. ; Sierra-Marquez, J.FZJ* ; Guzman, G.FZJ* ; Franzen, A.FZJ* ; Willuweit, A.FZJ* ; Katona, I. ; Hidalgo, P.FZJ* ; Fahlke, C.FZJ* ; Guzman, R. E. (Corresponding author)FZJ*

2022
Soc. Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/32037  doi:10.1523/JNEUROSCI.2439-21.2022

Abstract: ClC-3, ClC-4, and ClC-5 are electrogenic chloride/proton exchangers that can be found in endosomal compartments of mammalian cells. Although the association with genetic diseases and the severe phenotype of knock-out animals illustrate their physiological importance, the cellular functions of these proteins have remained insufficiently understood. We here study the role of two Clcn3 splice variants, ClC-3b and ClC-3c, in granular exocytosis and catecholamine accumulation of adrenal chromaffin cells using a combination of high-resolution capacitance measurements, amperometry, protein expression/gene knock out/down, rescue experiments, and confocal microscopy. We demonstrate that ClC-3c resides in immature as well as in mature secretory granules, where it regulates catecholamine accumulation and contributes to the establishment of the readily releasable pool of secretory vesicles. The lysosomal splice variant ClC-3b contributes to vesicle priming only with low efficiency and leaves the vesicular catecholamine content unaltered. The related Cl−/H+ antiporter ClC-5 undergoes age-dependent downregulation in wild-type conditions. Its upregulation in Clcn3−/− cells partially rescues the exocytotic mutant defect. Our study demonstrates how different CLC transporters with similar transport functions, but distinct localizations can contribute to vesicle functions in the regulated secretory pathway of granule secretion in chromaffin cells.

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Contributing Institute(s):

1. Physik der Medizinischen Bildgebung (INM-4)
2. Molekular- und Zellphysiologie (IBI-1)
3. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)
2. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2022

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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